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Efficacy and Safety of Gemcabene in Patients With Homozygous Familial Hypercholesterolemia on Stable, Lipid-Lowering Therapy (COBALT-1)

This study is currently recruiting participants.
See Contacts and Locations
Verified October 2016 by Gemphire Therapeutics, Inc.
Sponsor:
Information provided by (Responsible Party):
Gemphire Therapeutics, Inc.
ClinicalTrials.gov Identifier:
NCT02722408
First received: March 12, 2016
Last updated: October 27, 2016
Last verified: October 2016
  Purpose
The purpose of this study is to assess the efficacy, safety, and tolerability of multiple doses of Gemcabene in patients with HoFH on stable, lipid-lowering therapy.

Condition Intervention Phase
Hypercholesteremia Drug: Gemcabene 300 mg Drug: Gemcabene 600 mg Drug: Gemcabene 900 mg Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Open-Label, Dose-Finding Study to Assess the Efficacy, Safety, and Tolerability of Gemcabene in Patients With Homozygous Familial Hypercholesterolemia on Stable, Lipid Lowering Therapy (COBALT-1)

Resource links provided by NLM:


Further study details as provided by Gemphire Therapeutics, Inc.:

Primary Outcome Measures:
  • LDL-C [ Time Frame: Baseline and 28, 56, and 84 days ]
    Percent change from baseline


Secondary Outcome Measures:
  • non-HDL-C [ Time Frame: Baseline and 28, 56, and 84 days ]
    Percent change from baseline

  • Total Cholesterol [TC] [ Time Frame: Baseline and 28, 56, and 84 days ]
    Percent change from baseline

  • Triglycerides [TG] [ Time Frame: Baseline and 28, 56, and 84 days ]
    Percent change from baseline

  • HDL-C [ Time Frame: Baseline and 28, 56, and 84 days ]
    Percent change from baseline

  • Very low-density lipoprotein [VLDL-C] [ Time Frame: Baseline and 28, 56, and 84 days ]
    Percent change from baseline

  • hsCRP [ Time Frame: Baseline and 28, 56, and 84 days ]
    Percent change from baseline

  • Fibrinogen [ Time Frame: Baseline and 28, 56, and 84 days ]
    Percent change from baseline

  • Lipoprotein(a) [ Time Frame: Baseline and 28, 56, and 84 days ]
    Percent change from baseline

  • Apolipoprotein B (ApoB) [ Time Frame: Baseline and 28, 56, and 84 days ]
    Percent change from baseline

  • Apolipoprotein A-1 (ApoA-1) [ Time Frame: Baseline and 28, 56, and 84 days ]
    Percent change from baseline

  • Apolipoprotein A-II (ApoA-II) [ Time Frame: Baseline and 28, 56, and 84 days ]
    Percent change from baseline

  • Apolipoprotein C-II (ApoC-II) [ Time Frame: Baseline and 28, 56, and 84 days ]
    Percent change from baseline

  • Apolipoprotein C-III (ApoC-III) [ Time Frame: Baseline and 28, 56, and 84 days ]
    Percent change from baseline

  • Apolipoprotein E(ApoE) [ Time Frame: Baseline and 28, 56, and 84 days ]
    Percent change from baseline

  • Adverse Events [ Time Frame: 84 days ]
  • Clinical Laboratory [ Time Frame: 84 days ]

Estimated Enrollment: 8
Study Start Date: May 2016
Estimated Study Completion Date: February 2017
Estimated Primary Completion Date: February 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Gemcabene 300 mg QD
Gemcabene treatment on stable background statin therapy
Drug: Gemcabene 300 mg
1-300 mg tablet, QD, 28 days
Experimental: Gemcabene 600 mg QD
Gemcabene treatment on stable background statin therapy
Drug: Gemcabene 600 mg
2-300 mg tablets, QD, 28 days
Experimental: Gemcabene 900 mg QD
Gemcabene treatment on stable background statin therapy
Drug: Gemcabene 900 mg
3-300 mg tablets, QD, 28 days

  Eligibility

Ages Eligible for Study:   17 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Provision of written and signed informed consent (by patient or legal guardian) prior to any study-specific procedure;
  • Male or female ≥17 years of age at time of consent;
  • Diagnosis of HoFH by genetic confirmation (including compound heterozygosity) or a clinical diagnosis based on either (1) a history of an untreated LDL-C concentration >500 mg/dL (12.92 mmol/L) together with either appearance of xanthoma before 10 years of age, or evidence of heterozygous familial hypercholesterolemia in both parents or, if history is unavailable, (2) LDL-C >300 mg/dL (7.76 mmol/L) on maximally tolerated lipid-lowering drug therapy;
  • Currently on a stable, low-fat, low-cholesterol diet in combination with a pre-existing, regulatory-approved, not excluded lipid-lowering therapy (i.e., statins, monoclonal antibodies to PCSK9, cholesterol absorption inhibitors, bile acid sequestrants, or nicotinic acid, or any combination thereof) at a stable dose for at least 4 weeks prior to the Screening Visit;
  • Fasting LDL-C value >130 mg/dL (3.36 mmol/L) at the Screening Visit;
  • Physical examination, including vital signs, that is within normal limits or clinically acceptable to the Investigator;
  • Weight ≥50 kg;
  • Female patients must not be pregnant or lactating. Women of child-bearing potential must have a negative serum pregnancy test at the Screening Visit and negative urine dipstick on Day 1 prior to dosing in order to qualify for the study. Women who are surgically sterile or are clinically confirmed to be post-menopausal (i.e., documented amenorrhea for ≥1 year in the absence of other biological or physiological causes) are not considered to be of child-bearing potential; and
  • Women of child-bearing potential must agree to use acceptable methods of contraception throughout the duration of the study and for 30 days after the last dose of study drug. For this study, double-barrier contraception is required.

Exclusion Criteria:

  • Other forms of primary hyperlipoproteinemia and secondary causes of hypercholesterolemia (e.g., nephrotic syndrome or hypothyroidism);
  • Abnormal liver function test at the Screening Visit (aspartate aminotransferase or alanine aminotransferase >2 × the upper limit of normal [ULN]; total bilirubin >1.5 × ULN; or alkaline phosphatase >2 × ULN based on appropriate age and gender normal values). Patients with bilirubin >1.5 × ULN and history of Gilbert's syndrome may be included; reflexive direct bilirubin testing will be used to confirm Gilbert's syndrome;
  • Moderate (Grade B) or severe (Grade C) chronic hepatic impairment according to the Child Pugh classification;
  • Active liver disease (e.g., cirrhosis, alcoholic liver disease, hepatitis B virus [HBV], hepatitis C virus [HCV], autoimmune hepatitis, liver failure, liver cancer), history of liver transplant, or known diagnosis of human immunodeficiency virus (HIV);
  • Triglycerides value >400 mg/dL (4.52 mmol/L) at the Screening Visit;
  • Moderate to severe renal insufficiency defined as an estimated GFR <30 mL/min/1.73m2 (calculated using The Chronic Kidney Disease Epidemiology Collaboration equation) at the Screening Visit;
  • Abnormal urinalysis (proteinuria greater than trace or any male or non-menstruating female with greater than trace hematuria), confirmed by reflexive urine protein:creatinine ratio testing;
  • Uncontrolled thyroid disease: hyperthyroidism or hypothyroidism as defined by thyroid stimulating hormone (TSH) below the lower limit of normal or >1.5 × ULN, respectively, at the Screening Visit. If controlled, treatment should be stable for at least 3 months prior to the Screening Visit;
  • Type 1 diabetes mellitus or uncontrolled type 2 diabetes mellitus (hemoglobin A1c [HbA1c] value >8%), or any diabetic patient taking insulin and/or thiazolidinediones;
  • New York Heart Association Class III or IV heart failure;
  • Myocardial infarction, severe or unstable angina pectoris, coronary angioplasty, coronary artery bypass graft, or other major cardiovascular events resulting in hospitalization within 3 months of the Screening Visit. Patients with adequately treated stable angina, per Investigator assessment, may be included;
  • Uncontrolled cardiac arrhythmia or prolonged QT on the Screening Visit or Day 1 prior to dosing ECG (QTcF >450 msec for men and >470 msec for women) or known family history of prolonged QT or unexplained sudden cardiac death;
  • Uncontrolled hypertension, defined as sitting systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg, and confirmed by repeat measurement;
  • Currently receiving cancer treatments or, in the Investigator's opinion, at risk of relapse for recent cancer;
  • Use of fibrate lipid-lowering agent 6 weeks prior to the Screening Visit;
  • Hypersensitivity to or a history of significant adverse reactions to any fibrate lipid lowering agent;
  • Use of apheresis (LDL or plasma) 8 weeks prior to the Screening Visit;
  • Use of lomitapide 2 months prior to the Screening Visit;
  • Use of mipomersen 5 months prior to the Screening Visit;
  • Use of any excluded medications or supplements (e.g., potent cytochrome P450 [CYP] 3A4 inhibitors);
  • History of drug or alcohol abuse within the past year or inability to comply with protocol requirements, including subject restrictions;
  • Previously treated with gemcabene;
  • Participation in another clinical study of an investigational agent or device concurrently or within 1 month prior to the Screening Visit, or use of an investigational agent within 1 month or 5 half-lives (if known), whichever is longer, prior to the Screening Visit; or
  • Any other finding which, in the opinion of the Investigator, would compromise the patient's safety or participation in the study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02722408

Contacts
Contact: Liz Masson lmasson@gemphire.com

Locations
United States, California
Westside Medical Associates of Los Angeles Recruiting
Beverly Hills, California, United States
Contact: Norman Lepor, MD    310-289-9955    norman.lepor@gmail.com   
Canada, Ontario
Robarts Research Institute Recruiting
London, Ontario, Canada
Contact: Robert Hegele, MD    519-931-5271    hegele@robarts.ca   
Canada, Quebec
Ecogene-21 Recruiting
Chicoutimi, Quebec, Canada
Contact: Daniel Gaudet, MD    428-541-1077    daniel.gaudet@umontreal.ca   
Montreal Heart Institute Recruiting
Montreal, Quebec, Canada
Contact: Jean-Claude Tardiff, MD    514-376-3300    jean-claude.tardiff@icm-mhi.org   
Israel
Wolfson Medical Center Internal Medicine Dept. Recruiting
Holon, Israel
Contact: Dov Gavish, MD    +972-3-5028-644    gavish@wolfson.health.gov.il   
Center for Research, Prevention and Treatment of Atherosclerosis - Cardiology Department of Medicine Kiryat Hadassah Recruiting
Jerusalem, Israel
Contact: Ronen Durst, MD       durst@hadassah.org.il   
Ziv Medical Center Internal Medicine Department Recruiting
Safed, Israel
Contact: Osama Hussein, MD    +972-4-6828114    osama.h@ziv.health.gov.il   
Sponsors and Collaborators
Gemphire Therapeutics, Inc.
  More Information

Responsible Party: Gemphire Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT02722408     History of Changes
Other Study ID Numbers: GEM-201
Study First Received: March 12, 2016
Last Updated: October 27, 2016

Keywords provided by Gemphire Therapeutics, Inc.:
LDL-C
Lipid Regulator

Additional relevant MeSH terms:
Hypercholesterolemia
Hyperlipoproteinemia Type II
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Hyperlipoproteinemias
Cobalt
Trace Elements
Micronutrients
Growth Substances
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 24, 2017